Cyanides and Cyanogens

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Cyanides and Cyanogens

• Stevan Cordas DO MPH. Committee on Bioterrorism.
  Texas Department of Health

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Types of Cyanides

• Hydrogen cyanide gas (AC)
• Water soluble types
• Potassium cyanide
• Sodium cyanide
• Water insoluble types
• Mercury cyanates
• Gold and silver cyanates

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Other Sources of Cyanide

• Nitroprusside
• Cyanogen chloride (CK)
• Cyanogen bromide (CB)
• Sodium nitroprusside
• Laetrile (I Gm 60 mg CN), chokeberries
• Bitter Almond, apricot and other fruit pits
• Cassava - Linked to tropical ataxic neuropathy.
  Konzo Upper motor neuron disease

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Sources of Cyanide

• Available without a prescription
• Rodenticides, Insecticides
• Silver and metal polishing solutions
• Fumigating products
• Photographic development solutions
• Tanning and electroplating industries
• Metallurgy - jewelers

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History of Cyanides

• Used as a potion to kill friends and enemies
  since ancient Rome.
• Isolated and identified by Sheele 1784.
• Continues to be used in the gas chamber as
  potassium cyanide dropped into dilute sulfuric
  acid. Still popular in murder and suicide.
• Used by France 1915-16 as hydrogen cyanide gas.
  Called AC by military.

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History of Cyanide (Cont.)

• Cyanogen chloride, also called CK by the
  military, introduced September 1916.
• Austrians tried cyanogen bromide about the same
  time.
• In WWII millions of civilians and captured
  soldiers died from hydrocyanic acid adsorbed on a
  dispersible base (Zyklon B), a rodenticide.
• Aum Shinrikyo 1995 attempt to kill more in Tokyo.

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Additional History

• Who will forget the Jonestown massacre or the
  Tylenol deaths?
• Cause of toxic amblyopia for tobacco originated
  cyanide.
• Congenital flaw in cyanide metabolism lead to
  Lebers Optic Atrophy.

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Facts About Cyanides

• 50 mg of the gas and 500mg of the sodium or
  potassium salts is lethal.
• Cigarette smoke contains 0.041 ?g/ml whole blood.
  0.016 ?g/ml in Controls.
• Inhalation of gas kills in seconds. Longer period
  with the soluble gt insolublegt cyanogen salts.
  Skin absorption is possible with this agent.
• Italian authorities arrested an Al Quaeda cell it
  Italy with 9 lbs of potassium cyanide intending
  to poison the water of the US Embassy.

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Pathophysiology

• Rapidly enters the blood through breath,
  intestine or skin.
• Cases histotoxic hypoxia by interfering with the
  respiratory cytochrome oxidase system. Greatest
  affinity for oxidized Iron at the cytochrome a-a3
  complex.
• TWA 8 hours in US is 10 ppm. 100 ppm will kill in
  one hour. 300 ppm will kill in minutes.
• CN is an important killer in fires.

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Clinical Manifestations of Cyanide Poisoning

• If not fatal, we see weakness of the legs,
  vertigo, headache and nausea.
• This may be followed by convulsions and death. At
  a high Concentration Time level (Ct), death will
  occur in 20 seconds. It is unlikely that you will
  encounter any of those cases. The survivors
  should be observed and if symptomatic treated.

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Clinical Manifestations of Cyanide Poisoning

• Gasping for air, hypertensive, bradycardic.
• Bulging eyes.
• Odor of bitter almonds - faint. 20-40 cant
  smell it.
• Cold clammy skin May have cherry red skin.
  Cyanosis late.
• Venous blood the same color as arterial blood
  bright red or cherry pink.
• May look inebriated, confused, dizzy, nauseated.
  Chest pain.

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Odors of Some Chemical Weapons

• Nerve gas None to fruity or paint-like.
• Mustard Garlic or Horseradish.
• Lewisite Fruity to germanium.
• Phosgene New mown hay or green corn.
• Cyanide Bitter almond (faint).

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Diagnosis of Cyanide Poisoning

• Clinical diagnosis mainly. CYANTOSNO paper.
• Blood cyanide of 0.2 ?g/ml Clinical toxicity
  begins.
• Blood cyanide of 1.0 to 2.5 ?g/ml stupor and
  agitation. Levels over 2.5 ?g/ml potentially
  fatal.
• Pulse oximetry not useful.
• Draw arterial and venous oxygen saturation. If
  less than 10 mm Hg suspect cyanide.
• Look for elevated lactate and metabolic acidosis.
  Plasma lactate gt 6 mmol/L.

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Treatment of Cyanide Poisoning

• Use Lilly cyanide antidote kit.
• Manage ABC of emergency care.
• Remove from agent and remove any liquid cyanide
  that is present with water. Irrigate eyes for 10
  minutes if required. Wear MOPP4 of Level A
  protection at first. Skin contamination is not
  required for the gas.
• Intubate. Administer 100 Oxygen.
• Keep warm and Quiet.
• No mouth to mouth resuscitation.

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Treatment of Cyanide Poisoning

• First you must rapidly bind or fixate the cyanide
  ion either by creating methemoglobin or fixing it
  with cobalt compounds. Any person who is
  conscious and breathing normally more than 5
  minutes after being exposed to and removed from
  cyanide agents will recover without any treatment
  as this substance is rapidly detoxified by the
  body.

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Treatment of Cyanide Poisoning

• Amyl nitrite is often used if there is a
  respiratory positive pressure present. Do not use
  amyl nitrate with oxygen as an explosion may
  occur. Follow this with sodium thiosulphate. In
  the military amyl nitrate is used less than in
  the civilian sector. More meaningful and
  predictable levels of methemoglobin can be
  produced by sodium nitrate.

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Treatment of Cyanide Poisoning

• Administer the sodium thiosulphate at a dose of
  12.5 Gms (50 cc of a 50 solution over a 10
  minute period of time.
• Remember that methemoglobin levels higher than
  10 usually indicate that further nitrates are
  not needed. Cardiac complications with higher
  doses.

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Treatment of Cyanide Poisoning

• If there is impairment with breathing, IV sodium
  nitrate should be used (10 cc of a 3 solution,
  300mg over 3 minutes). This will produce
  methemoglobin, which binds the cyanide. Keep the
  patient flat or their blood pressure will fall
  from the nitrite. Try to obtain a little cyanosis
  to indicate methemoglobinemia.

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Treatment of Cyanide Poisoning

• Another alternative way to initially bind cyanide
  is with intravenous hydroxycyanocobalamine. This
  is commercially available but large amounts (4 g)
  IV slowly should be used as compared to the IM
  route. The cobalt will act to bind a portion of
  the cyanide and complex it until the thiosulphate
  is employed to finish the job. Hydroxy B12 is
  relatively safe. Disadvantages include rare
  allergic reaction, high cost for the amounts
  required, short half-life as it decomposes in
  light.

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Treatment of Cyanide Poisoning

• Remember that sodium thiosulphate must always be
  given to complete the medical detoxification of
  cyanate by converting the free and bound cyanide
  to thiocyanates under the influence of the enzyme
  rhodenase. The relatively nontoxic thiocyanates
  can be metabolized.

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Treatment of Cyanide Poisoning

• There are four methods in the human to detoxify
  cyanide. The most effective of these is via
  rhodenase but it is rate limited by a rapid
  decline in sulfur containing substrate.
  Thiocyanate is the natural product of this
  process. The addition of more thiocyanate helps
  improve this process by adding sulfur molecules.

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Summary

• Protect yourself.
• Learn the agent and treatment.
• You can make a difference.
• Dont treat mild cases.
• Treatment symptomatic cases aggressively.

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